ME Association to fund fourth study into the role of the mitochondria in ME/CFS

We are pleased to announce that our Ramsay Research Fund is about to
start funding another research study relating to the role of mitochondria in
ME/CFS. This research grant has been given to Dr Karl Morten and Professor
Joanna Poulton at the University of Oxford.

The following description of the
background to the Oxford research and what will it involve has been prepared by
Dr Karl Morten:

Is aberrant mitochondrial function a major player in CFS/ME?

Mitochondria are well known for
their role as the ‘power house of the cell’. But they also have a diverse range
of other functions.

These include a role in
programming cell death, synthesis of cellular building blocks, cell-signalling
and more recently a potential role in cellular immunity (West et al 2015).

Control of mitochondrial number,
quality and structure is a highly regulated process varying between cells and
tissues.

The fatigue seen in CFS/ME
patients and the post-exertional malaise observed in the majority of patients
has led to the proposal that a failure in the energy generation/supply system
at a cellular level may play a role in the disease.

Over the last 20-30 years,
attempts by researchers using techniques successfully applied to identify
mitochondrial defects in patients with genetic defects in the mitochondrial
respiratory chain have consistently failed to identify mitochondrial abnormalities
in CFS/ME patients.

Between, 2009-2013 a series of
papers by Booth/Myhill et al [2-4] have demonstrated an interesting correlation
between the level of mitochondrial dysfunction in a specific type of white
blood cell called a neutrophil and the severity of disease in ME/CFS patients.

In addition to measuring total
cellular energy in the form of a chemical called adenosine triphosphate (ATP)
the authors use novel approaches to measure the ability of mitochondria to
regenerate ATP following depletion of mitochondria ATP with the electron
transfer chain (ETC) inhibitor sodium azide.

Such an approach is claimed to be
a major advance on current approaches which just measure steady state levels of
ATP and adenosine diphosphate (ADP) in isolated organelles or whole cells.

As steady state ATP levels are a
consequence of supply and demand they do not always reflect the ability of
mitochondria to generate ATP.

MEA project grant (5 months):

Establishing protocols to assess mitochondrial function in Neutrophils
and Monocytes from ME/CFS patients.

The current pilot study is to set up the tests required to assess
mitochondrial function in blood samples from ME/CFS patients.

For this we will use cell models with known mitochondrial dysfunction
and bio-energetic impairment to both validate and improve on the tests
developed by Acumen [2-4].

Our goal is to develop a method to assess mitochondrial function
compatible with the widely used Seahorse Biosciences metabolic flux analyzer
and plate based fluorescent probe oxygen and pH measuring platforms.

This will make the blood tests more globally accessible to a wide range
of researchers allowing a more universal validation of the findings of
Booth/Myhill.

Other MEA RRF research involving mitochondria in ME/CFS.

The MEA Ramsay Research Fund has
been funding, or co-funding, three other research projects involving
mitochondrial function and testing mitochondrial function:

1 COMPARISON OF RESULTS FROM A
COMMERCIAL AND NHS BLOOD TEST TO ASSESS MITOCHONDRIAL FUNCTION

This study is comparing the
results of a commercial blood test for mitochondrial function that has been
developed by Dr Sarah Myhill and colleagues with the results from an
international and widely accepted test of mitochondrial function that has a
long and successful track record in clinical diagnosis and research of muscle
disease particularly in the UK.

The aim is to determine the
efficacy of each set of tests in relation to ME/CFS. In the exciting case that
a synergy between the two diagnostic approaches exists, it is hoped that this
preliminary study will promote an investigation into a more inclusive and
highly resolved analytical technique for metabolic testing of people with
ME/CFS.

2 ABNORMALITIES IN MITOCHONDRIAL
FUNCTION IN SKELETAL MUSCLE (CO-FUNDED WITH THE MEDICAL RESEARCH COUNCIL)

Employing new technology, this
research aims to demonstrate that skeletal muscle mitochondria are
dysfunctional and cause the muscle fatigue experienced in ME/CFS:

‘The dysfunctional mitochondria
then activate a process which leads to a chronic, low grade inflammation,
commonly reported in patients with CFS, which in turn results in further
mitochondrial abnormalities and the establishment of a vicious circle of
events. Understanding the processes by which muscle fatigue occurs will lead to
optimal interventions that break this vicious circle and improve muscle
function and wellbeing of individuals.’ Extract
taken from: MRC CFS/ME Current Projects

Preliminary results from the
study were published in a recent paper: ‘The Role of Cytokines in Muscle Fatigue
in Patients with Chronic Fatigue Syndrome’, The FASEB Journal, April 2015.

The authors recruited 100
untreated patients with CFS and 100 age and sex matched healthy controls, and
concluded:

‘…a sub-group of patients with
CFS may have low level inflammation and analyses are underway to further
characterise other inflammatory markers in serum and muscle of these patients
and to determine whether such changes could affect indices of muscle function
or central fatigue.’

Lead researcher: Professor Anne
McArdle

This research is being jointly
funded with the Medical Research Council

RRF investment = £30,000

3 PATTERNS OF MITOCHONDRIAL DNA
VARIATION

This is an 18-month study that
began in May 2014 and seeks to determine if patterns of mitochondrial DNA variation
in ME/CFS are different than in healthy controls.

At the launch of the initiative,
Dr Joanna Elson commented:

“Mitochondria are the powerhouses
of the cell, and mitochondrial DNA provides the codes for proteins that are
essential for energy production. We want to see if patients with ME/CFS have
different patterns of mitochondrial DNA variation that could affect a person’s
chances of succumbing to ME/CFS, or act as a barrier to recovery.”

About Me

I am a Christian, saved by grace alone through faith alone. I have had the neuroimmune disorder ME, Myalgic Encephalomyelitis, since 1991. From North Somerset, now in N. Ireland. Please see my website for further information about ME.